The major objective of this study is to develop a comprehensive understanding of the keratinization process in order to more fully understand the numerous disorders which involve epidermis, hair and nail. Since the fibrous protein play a major role emphasis will be placed on them, but other important structural components, keratohyalin and cornified cell envelope, will also be investigated. These studies will be done in whole tissue as well as in cultured epidermal cells with the aim of using epidermal cell culture to study the metabolic disturbances in a number of disorders of keratinization including psoriasis and several types of ichthyosis. Epidermal cell culture will be used to study mechanism of disease and the effect of various hormones and chemicals on normal epidermal cells as well as disease cells. This will include basal cell carcinoma. Nail matrix cells will be studied in culture and the products of differentiation will be compared to intact nail and epidermis. This will be started with cow hoof and then human tissue will be used. We will make antibodies to epidermal histidase and the arginine to citrulline converting enzymes in order to study epidermal cancer. This will be developed into a technique for diagnosing epidermal cancer. The epidermal arginine to citrulline enzyme will be investigated to elucidate the natural substrates, mechanism of action and products formed. We shall continue to study and collect inherited disorders of keratinization so that patient material will be available for laboratory study. We shall also expand our studies of synthetic retinoids on a number of inherited disorders of keratinization, including psoriasis.